Leukemia associated antigens have been detected on tumor cells of experimental animals by both serological and in vitro cellular immune reactions. Among those detected are fetal, differentiation, tissue specific, viral, virally specified and tumor associated transplantation antigens. It is not clear whether the serological and cellular immune tests detect the same or different antigens or moreover how these differences relate to the in vivo host resistance to the tumor. Even less clear is the antigenic makeup and host response to human leukemia patients despite a vigorous search by several investigators. Using mixed tumor cell lymphocyte culures (MTLC) and cell mediated cytotoxicity (LMC) assays, differences have been demonstrated between leukemia cells and autologous lymphocytes. Whether these differences function as tumor associated transplantation antigens and stimulate a host response to the tumor has not been established. The present studies are designed to define the antigenic specificities detected by the MTLC and LMC in comparison to serologically defined antigens using murine leukemias. Sera obtained from mice immunized with syngeneic or allogeneic tumors will be assayed for direct cytotoxicity and by quantitative absorption using different tumor cells, fetal cells and normal cells of different tissue types. Lymphocytes from these animals will be used as responder cells for MTLC and subsequently effector cells for LMC. The specificities detected by these assays can then be compared. The in vitro reactions will be correlated with in vivo function by adoptive transfer experiments and methods to augment tumor rejection using in vitro activated immunocompetent cells will be explored. Parallel experiments using human leukemia cells to establish the antigenic specificities and any cross reactivity will be interpreted using the murine systems as models. The object of these studies is to provide a rational basis for the interpretation of tests for tumor specific immunity and to explore new methods to augment tumor immune responses.